Radiolabelling of 1,4-disubstituted 3-[18F]fluoropiperidines and its application to new radiotracers for NR2B NMDA receptor visualization
Koudih, R; Gilbert, G; Dhilly, M; Abbas, A; Barré, L; Debruyne, D; Sobrio, F
HERO ID
1847847
Reference Type
Journal Article
Year
2012
Language
English
PMID
| HERO ID | 1847847 |
|---|---|
| In Press | No |
| Year | 2012 |
| Title | Radiolabelling of 1,4-disubstituted 3-[18F]fluoropiperidines and its application to new radiotracers for NR2B NMDA receptor visualization |
| Authors | Koudih, R; Gilbert, G; Dhilly, M; Abbas, A; Barré, L; Debruyne, D; Sobrio, F |
| Journal | Organic and Biomolecular Chemistry |
| Volume | 10 |
| Issue | 42 |
| Page Numbers | 8493-8500 |
| Abstract | In order to develop a novel and useful building block for the development of radiotracers for positron emission tomography (PET), we studied the radiolabelling of 1,4-disubstituted 3-[(18)F]fluoropiperidines. Indeed, 3-fluoropiperidine became a useful building block in medicinal chemistry for the pharmacomodulation of piperidine-containing compounds. The radiofluorination was studied on substituted piperidines with electron-donating and electron-withdrawing N-substituents. In the instance of electron-donating N-substituents such as benzyl or butyl, configuration retention and satisfactory fluoride-18 incorporation yields up to 80% were observed. In the case of electron-withdrawing N-substituents leading to carbamate or amide functions, the incorporation yields depend on the 4-susbtitutent (2 to 63%). The radiolabelling of this building block was applied to the automated radiosynthesis of NR2B NMDA receptor antagonists and effected by a commercially available radiochemistry module. The in vivo evaluation of three radiotracers demonstrated minimal brain uptakes incompatible with the imaging of NR2B NMDA receptors in the living brain. Nevertheless, moderate radiometabolism was observed and, in particular, no radiodefluorination was observed which demonstrates the stability of the 3-position of the fluorine-18 atom. In conclusion, the 1,4-disubstituted 3-[(18)F]fluoropiperidine moiety could be of value in the development of other radiotracers for PET even if the evaluation of the NR2B NMDA receptor antagonists failed to demonstrate satisfactory properties for PET imaging of this receptor. |
| Doi | 10.1039/c2ob26378e |
| Pmid | 23007637 |
| Wosid | WOS:000310215400015 |
| Is Certified Translation | No |
| Dupe Override | No |
| Comments | Scopus URL: https://www.scopus.com/inward/record.uri?eid=2-s2.0-84867340545&doi=10.1039%2fc2ob26378e&partnerID=40&md5=f814489b2c84188aaa8651cf08cf7674 |
| Is Public | Yes |
| Language Text | English |
| Keyword | Brain uptake; Building blockes; Electron-donating; Electronwithdrawing; Fluorine-18; Fluoropiperidine; In-vivo; Medicinal chemistry; NMDA receptor; PET imaging; Radiofluorination; Radiolabelling; Radiosynthesis; Amides; Electrons; Fluorine; Positron emission tomography; Radioactive tracers; fluorine; n methyl dextro aspartic acid receptor; NR2B NMDA receptor; piperidine derivative; animal; article; brain; chemistry; drug antagonism; metabolism; methodology; positron emission tomography; rat; scintiscanning; Animals; Brain; Fluorine Radioisotopes; Piperidines; Positron-Emission Tomography; Rats; Receptors, N-Methyl-D-Aspartate |